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机构地区:[1]广西中医学院第一附属医院肿瘤血液病科,广西南宁530021
出 处:《中华肿瘤防治杂志》2010年第15期1168-1171,共4页Chinese Journal of Cancer Prevention and Treatment
摘 要:目的:研究大蒜素对肿瘤中血管内皮生长因子(VEGF)及其上游调节基因HIF-1α表达的影响,并探讨其抑制肿瘤生长的机制。方法:皮下荷瘤小鼠体内注射不同剂量的大蒜素,监测肿瘤生长情况;处死小鼠后以ELISA法检测小鼠血清VEGF的表达;realtime-PCR法检测肿瘤中VEGF和HIF-1αmRNA的表达;免疫组化法检测肿瘤中CD34的表达并量化微血管数;蛋白质印迹法检测HIF-1α蛋白的表达。结果:不同剂量大蒜素均对小鼠皮下肿瘤生长有抑制作用,且呈剂量依赖关系。低、高剂量大蒜素对肿瘤的抑制作用与对照组相比分别为71.4%和40.8%;小鼠体内以及肿瘤处的VEGF表达都显著降低,与对照组相比分别为64.5%和62.9%(血清)、34.6%和32.3%(瘤内);同时HIF-1α蛋白表达亦降低,分别是对照组的26.7%和25.1%;肿瘤组织中的CD34表达也明显减少,与对照组相比分别为16.8%和14.4%,P<0.01。结论:大蒜素可以通过抑制肿瘤VEGF的生成,进而抑制肿瘤血管的形成,可能是通过先阻断VEGF的上游调控基因HIF-1的表达来实现的,这为肿瘤临床药理学研究提供一定的理论基础。OBJECTIVE:To investigate the effect of allicin on tumor vascular endothelial growth factor (VEGF) and its upstream regulator HIF-1α gene expression,to explore its mechanism of inhibiting tumor growth.METHODS:The tumor-bearing mice were injected subcutaneously with different doses of allicin,to monitor the tumor growth;the ELISA assay was used to detect the expression of VEGF in serum;realtime-PCR was used to detect the expression of VEGF,HIF-1α mRNA in tumor tissue;Immunohistochemistry was used to detect the expression of CD34 and to quantify the number of microvessels in tumor;Western blot was used to detect HIF-1α protein expression.RESULTS:Different doses of allicin could inhibit the tumor growth in mice and demonstrate the property of dose-dependent.Compared with the control group,the weight of low and high-dose groups were 71.4% and 40.8% respectively;the expression of VEGF mRNA were decreased obviously and were 64.5% and 62.9% reseparately in serum and 34.6%,32.3% respectively in tumor tissue.At the same time the expression of HIF-1α also reduced and were 26.7% and 25.1% compared with the controls.The expression of the CD34 were significantly reduced in tumor and were 16.8% and 14.4% respectively (P〈0.01).CONCLUSIONS:Allicin can inhibit tumorgrowth through inhibiting the VEGF expression and then inhibiting tumor angiopoiesis.This inhibitory effect may be through blocking the expression of,upstream regulation gene of VEGF,HIF-1α firstly to achieve.This research provides a theoretical basis for tumor clinical pharmacology studies.
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